GATE Monte Carlo approach to heterogeneity dose distribution in small fields used in radiation therapy.

The Accurate dosage prediction in Radiation Therapy is challenging, prompting a need for precision beyond conventional clinical Treatment Planning Systems (TPS). Monte Carlo-based methods are sought for their superior accuracy. The aim of this study is to compare dose distributions between the ACUROS algorithm and the GATE platform in various tissue densities and field sizes, focusing on smaller fields. This study was initiated with a homogeneous validation of the TrueBeam STX system, using measurements obtained from the Centre Hospitalier Interregional Edith Cavell (CHIREC) in Brussels. The validation compared dosimetric functions (Percentage Depth Dose (PDD), Dose profile (DP) and Collimator scatter fraction (CSF)) employing the GAMMA index with a 2% / 2 mm criterion tolerance. Following this, heterogeneous studies examined dose distributions between the ACUROS algorithm and the GATE platform in various tissue densities and field sizes, with a specific focus on smaller fields. Simulations were conducted using both platforms on chest phantoms with heterogeneous slabs representing bone, lung, and heart, each housing a central tumor. The impact of electronic equilibrium on tumors for different small field sizes was evaluated. Results showed a remarkable 99% agreement between measurements and GATE calculations in the homogeneous validation of the TrueBeam STX system. However, in heterogeneous studies, ACUROS consistently overestimated lung doses by up to 8% compared to GATE simulation, especially evident with a flattening filter and smaller beam sizes at density interfaces. This highlights significant dose estimation discrepancies between ACUROS and GATE, emphasizing the need for precise calculations. The findings support exploring Monte Carlo-based methods for enhanced accuracy in Radiation Therapy treatment planning.

[Chemical peritonitis complicating the spontaneous rupture of a dermoid cyst of the ovary]. / Péritonite chimique compliquant la rupture spontanée d'un kyste dermoïde de l'ovaire.

Mature ovarian teratoma is the most frequent benign tumor in premenopausal women. It is usually asymptomatic but complications are possible such as adnexal torsion, infection, malignant transformation or cystic rupture. The latter can be spontaneous or more often occurs during surgery of excision of dermoid cyst. It can rarely result in chemical peritonitis, which is due to the irritation of the peritoneal serosa by the aseptic content of the tumour. We report the case of a patient who undrewent an emergency laparotomy for a chemical peritonitis following a spontaneous rupture of a dermoid cyst. Afterwards, she developed an acute respiratory distress syndrome that required an admission in the intensive care unit and subsequent surgery.

Le tératome mature de l'ovaire est la tumeur ovarienne bénigne la plus fréquente chez la femme en pré-ménopause. Le plus souvent, il est asymptomatique, mais il peut se compliquer par une torsion annexielle, une infection, une dégénérescence maligne ou une rupture kystique. Celle-ci peut être spontanée ou, plus souvent, survenir lors d'une chirurgie d'exérèse du kyste. Rarement, elle peut entraîner une péritonite chimique. Celle-ci est consécutive à l'irritation de la séreuse péritonéale par le contenu aseptique da la tumeur. Nous rapportons ici le cas d'une patiente opérée en urgence pour une péritonite chimique suite à une rupture spontanée d'un kyste dermoïde. Dans les suites opératoires, la patiente a développé un syndrome de détresse respiratoire aigu qui a nécessité une prise en charge aux soins intensifs et une nouvelle intervention chirurgicale.

[Comparing two screening policies of gestational diabetes mellitus: The Mohammed V Training Military Hospital of Rabat (Morocco)]. / Comparaison de deux politiques de dépistage du diabète gestationnel: expérience de l'hôpital militaire d'instruction Mohammed V de Rabat (Maroc).

OBJECTIVES: We wanted to measure the impact of going from a two-step screening for gestational diabetes mellitus (50g oral glucose tolerance test then 100g OGTT) to a one-step screening 75g OGTT (WHO's recommendations). PATIENTS AND METHODS: A prospective study was carried out among patients who consulted between July 1st, 2008 and October 31st, 2009. The screening was performed in the first trimester if risk factors were identified and between 24 and 28 weeks of gestation (WG). RESULTS: During our period of study of 15 months, 706 pregnant women were included. The prescription of a screening test was performed in 403 women, i.e. 57% of cases. Out of the 403-screened women, 33 had gestational diabetes mellitus (GDM) i.e. a 8.2% prevalence rate. In univariate analysis, the following are considered to be risk factors: age, diabetes family history and macrosomia history in a previous pregnancy. Between 24 and 28 WG, 34.34% of the screening tests were achieved. The 75g OGTT is prescribed in 96.2% of cases as a screening test of GDM but fasting blood glucose is still prescribed in 3.8% of cases. Also, before 12 WG, 75g OGTT represent 64.7% of the prescribed tests. DISCUSSION: Despite the simplification of the GDM screening procedure, our work shows no significant difference of the screening rate and prevalence of GDM between our present study and the first work done in the same service (57% versus 61%, P=0.7 and 8.2% versus 7.7%, P=0.9). The GDM risk factors found are also identical between the two studies: age, type 2 diabetes family history and macrosomia history. Moreover, there is a statistically significant improvement in the screening age (23±6.7 versus 20.9 WG±6.8 in the first half of 2008, P<0.001) and the number of tests ordered during the period between 24 and 28 WG (34.34% versus 23.9% in the first half of 2008, P<0.001). For the GDM screening tests between 24 and 28 WG, 75g OGTT replaced the 50g OGTT (test used in the first study), but fasting blood glucose is prescribed in 3.8% of cases knowing that normal fasting blood glucose alone done between 24 and 28 WG has a poor sensitivity and do not exclude the diagnosis of GDM (Cosson, 2006) [11]. Also, before 12 WG, 75g OGTT represents 64.7% of the prescribed tests. However, there is to date no data to validate load testing before 24 WG. CONCLUSION: Our comparative study revealed maintenance of low implementation of universal screening of GDM despite the simplification of the protocol. Between 24 and 28 WG, 75g OGTT replaced the 50g OGTT, but fasting blood glucose was still prescribed. A sensitization meeting involving all intervening persons is to be organized with proposals for corrective actions. The final objective is the systematic screening of gestational diabetes mellitus with the use of fasting blood glucose in the first trimester and the 75g OGTT between 24 and 28 weeks of gestation.

Theoretical study of the fibrous capsule tissue growth around a disk-shaped implant.

We analyze the mathematical properties of the fibrous capsule tissue concentration around a disk-shaped implant. We establish stability estimates as well as monotonicity results that illustrate the sensitivity of this growth to the biocompatibility index parameters of the implant. In addition, we prove that the growth of the tissue increases exponentially in time toward an asymptotic regime. We also study the mathematical properties of the solution of the inverse problem consisting in the determination of the values of the biocompatibility index parameters from the knowledge of some fibrous capsule tissue measurements. We prove that this model calibration problem admits a unique solution, and establish a characterization of the index parameters. Furthermore, we demonstrate analytically that such a solution is not continuous with respect to the data, and therefore the considered inverse problem is ill-posed due to the lack of the stability requirement.

[Non ST elevation acute coronary syndromes and normal coronary angiography: is it truly good news?]. / Coronarographie normale au cours des syndromes coronariens aigus non ST+: une fausse bonne nouvelle?

Among 10% of all patients presenting with non ST elevation acute coronary syndromes (ACS), coronary angiography do not show non lesions at all (50%) or mild atheromatous stenosis (50%). ACS without angiographic stenosis are more prevalent in female sex and young patients but can be seen in older ones and in men. Pathogenic mechanisms include acute evolution of vulnerable non-significant plaques and endothelial dysfunction. In hospital and mean term prognosis is not as benign as expected. Six months deaths and myocardial infarction incidence is around 6%. Numerous rehospitalizations due to ischemic recurrences are also very often seen. Therefore, such surprising coronary angiograms do not preclude a fair follow-up. These patients need a careful therapeutic strategy.

Human pancreatic ribonuclease presents higher endonucleolytic activity than ribonuclease A.

Analyzing the pattern of oligonucleotide formation induced by HP-RNase cleavage shows that the enzyme does not act randomly and follows a more endonucleolytic pattern when compared to RNase A. The enzyme prefers the binding and cleavage of longer substrate molecules, especially when the phosphodiester bond that is broken is 8-11 nucleotides away from at least one of the ends of the substrate molecule. This more endonucleolytic pattern is more appropriate for an enzyme with a regulatory role. Deleting two positive charges on the N-terminus (Arg4 and Lys6) modifies this pattern of external/internal phosphodiester bond cleavage preference, and produces a more exonucleolytic enzyme. These residues may reinforce the strength of a non-catalytic secondary phosphate binding (p2) or, alternatively, constitute a new non-catalytic phosphate binding subsite (p3).

Idiopathic colonic varices: an unusual cause of massive lower gastrointestinal hemorrhage.

Varices of the entire colon are very rare. This rare cause of massive lower gastrointestinal hemorrhage is almost invariably associated with cirrhosis of the liver and consequent hypertension or portal venous obstruction. We report about a patient with massive lower gastrointestinal bleeding from extensive colonic varices. Despite extensive investigation and a follow-up of 3 years, the etiology of the colonic varices could not be determined. Only a few cases of apparent idiopathic (familial or non-familial) colonic varices have been described. Recognition of this abnormality is important, however, because colonic varices may be the cause of recurrent, frequently massive lower gastrointestinal hemorrhage. A misleading endoscopic diagnosis can lead to inappropriate biopsies, resulting in major bleeding.

[Catalytic properties of recombinant pancreatic ribonuclease A-K7H]. / Kataliticke osobine rekombinantne pankreasne ribonukleaze A-K7H.

Pancreatic ribonuclease A is an enzyme that binds up ribonucleic acid (RNA) along the multiple binding subsites that essentially recognize the negatively charged phosphates of the substrate. It is endoribonuclease that catalyse depolimerization of single-stranded RNA. This work gives additional support to the existence of the phosphate-binding site p2 and confirms the central role of Lys-7 in establishing and electrostatic interraction with a phosphate group of the substrate. In this work catalytic properties of recombinant ribonuclease K7H have been studied. This enzyme is a mutant enzyme which contains histidine instead of lysine in a position 7, amino-acid that participates in the main catalytic center of RNase A, named p1. It was obtained by site-directed mutagenesis. Kinetic parameters of K7H have determined with C > p i poli (C) as substrates at pH 5.5 i 7.5. Kinetic parameters of K7H for C > p and as a substrate at pH 5.5 have not altered, but at pH 7.5 were significantly increased. Value Km was also increased, that indicates decreasing of affinity. Increasing of catalysis was double. Results of kinetic parameters of K7H with poli (C) as a substrate in pH 5.5 have shown slight difference according to kinetic parameters of commercial RNase A with poli (C). Significant decreasing of values of all kinetic parameters for K7H were reaction at pH 7.5.

[Endonuclease activity of recombinant pancreatic nuclease (A-K7H)]. / Endonukleazna aktivnost rekombinantne pankreasne ribonukleaze A-K7H.

Pancreatic ribonuclease A (RNase A) is a endonuclease that catalyzes depolymerization of ribonucleic acid (RNA) releasing oligonucleotides. In the process of binding enzyme with substrate are involved several non-catalytic phosphate binding subsites, one of them is p2, additional to main catalytic site p1. RNaza A prefers binding and cleavage of longer substrate molecules, and 3',5'-phosphodiester bond should be some six-seven residues apart from the end of molecules of the chain of RNA. In this work is analysed endonuclease activity of recombinant pancreatic RNase A (K7H), that in position seven instead of a lysine there is a histidine, amino acid residue that participates in main catalytic site p1. Mutant enzyme is obtained by site-directed mutagenesis by Kunkel. Results of this investigation have shown that substitution of lysine by histidine in position seven of RNase A has produced total deletion of p2 subsite, and K7H has lost endonuclease activity, and has become exonuclease. These results confirm central role of Lys-7 in establishing p2 subsite and endonuclease activity of pancreatic RNase A.

The contribution of noncatalytic phosphate-binding subsites to the mechanism of bovine pancreatic ribonuclease A.

The enzymatic catalysis of polymeric substrates such as proteins, polysaccharides or nucleic acids requires precise alignment between the enzyme and the substrate regions flanking the region occupying the active site. In the case of ribonucleases, enzyme-substrate binding may be directed by electrostatic interactions between the phosphate groups of the RNA molecule and basic amino acid residues on the enzyme. Specific interactions between the nitrogenated bases and particular amino acids in the active site or adjacent positions may also take place. The substrate-binding subsites of ribonuclease A have been characterized by structural and kinetic studies. In addition to the active site (p1), the role of other noncatalytic phosphate-binding subsites in the correct alignment of the polymeric substrate has been proposed. p2 and p0 have been described as phosphate-binding subsites that bind the phosphate group adjacent to the 3' side and 5' side, respectively, of the phosphate in the active site. In both cases, basic amino acids (Lys-7 and Arg-10 in p2, and Lys-66 in p0) are involved in binding. However, these binding sites play different roles in the catalytic process of ribonuclease A. The electrostatic interactions in p2 are important both in catalysis and in the endonuclease activity of the enzyme, whilst the p0 electrostatic interaction contributes only to binding of the RNA.

The subsites structure of bovine pancreatic ribonuclease A accounts for the abnormal kinetic behavior with cytidine 2',3'-cyclic phosphate.

The kinetics of the hydrolysis of cytidine 2',3'-cyclic phosphate (C>p) to 3'-CMP by ribonuclease A are multiphasic at high substrate concentrations. We have investigated these kinetics by determining 3'-CMP formation both spectrophotometrically and by a highly specific and quantitative chemical sampling method. With the use of RNase A derivatives that lack a functional p2 binding subsite, evidence is presented that the abnormal kinetics with the native enzyme are caused by the sequential binding of the substrate to the several subsites that make up the active site of ribonuclease. The evidence is based on the following points. 1) Some of the unusual features found with native RNase A and C>p as substrate disappear when the derivatives lacking a functional p2 binding subsite are used. 2) The kcat/Km values with oligocytidylic acids of increasing lengths (ending in C>p) show a behavior that parallels the specific velocity with C>p at high concentrations: increase in going from the monomer to the trimer, a decrease from tetramer to hexamer, and then an increase in going to poly(C). 3) Adenosine increases the kcat obtained with a fixed concentration of C>p as substrate. 4) High concentrations of C>p protect the enzyme from digestion with subtilisin, which results in a more compact molecule, implying large substrate concentration-induced conformational changes. The data for the hydrolysis of C>p by RNase A can be fitted to a fifth order polynomial that has been derived from a kinetic scheme based on the sequential binding of several monomeric substrate molecules.

The role of non-catalytic binding subsites in the endonuclease activity of bovine pancreatic ribonuclease A.

Bovine pancreatic ribonuclease A catalyzes the depolymerization of RNA. There is much evidence that several subsites, in addition to the main catalytic site, are involved in the formation of the enzyme-substrate complex. This work analyzes the pattern of oligonucleotide formation by ribonuclease A using poly(C) as substrate. The poly(C) cleavage shows that the enzyme does not act in a random fashion but rather prefers the binding and cleavage of the longer substrate molecules and that the phosphodiester bond broken should be 6-7 residues apart from the end of the chain to be preferentially cleaved by ribonuclease A. The results demonstrate the model of the cleavage of an RNA chain based on the cooperative binding between the multisubsite binding structure of ribonuclease A and the phosphates of the polynucleotide (Parés, X., Nogués, M. V., de Llorens, R., and Cuchillo, C. M. (1991) in Essays in Biochemistry (Tipton, K. F., ed) Vol. 26, pp. 89-103, Portland Press Ltd., London). The contribution to the enzymatic process of the non-catalytic phosphate-binding subsite (p2) adjacent to the catalytic center has been analyzed in p2 chemically modified ribonuclease A or by means of site-directed mutagenesis. In both cases deletion of p2 abolishes the endonuclease activity of ribonuclease A, which is substituted by an exonuclease activity. All these results support the role of the multisubsite structure of the enzyme in the endonuclease activity and in the catalytic mechanism.

Diffusion of proteins in Sepharose Cl-B gels.

The reduced diffusion coefficient, D/D0, of fluorescein-labelled globular proteins in the agarose gels Sepharose Cl-2B, 4B and 6B were measured by the FRAP method. Comparison of the partition coefficients of the native and the labelled proteins in the gel showed that the fluorescein residues did not introduce new interactions between the solute and the gel matrix. D/D0 decreased as a function of the Stokes radius. The variation of D/D0 as a function of the partition coefficient of the proteins in the gel did not agree with a previously published prediction. This is in contrast with the diffusion of globular proteins in ACA34 gel, in which the sieving matrix is made of cross-linked polyacrylamide.

Malformations in 10,000 consecutive births in Tunis.

Malformations were assessed in 10,000 consecutively born infants, dead or alive, at the Wassila Bourgiba Maternity Hospital in Tunis. The medical and social history including the rate of consanguinity was studied in the malformed group as well as in a control group of 229 infants. Three hundred and ninety-six infants were malformed; 248 had major malformations and 148 had minor ones. Thirteen per cent of the stillborn were malformed compared to 3.7% of the liveborn. The rates of most specific malformations were comparable to those in other studies but a relatively high rate of neural tube defects, 2.2/1000, can be noted. There is a significant overrepresentation of consanguinity (65%) in parents of non syndromic multi-malformed infants.

[Ganglioneuroblastoma of the orbit]. / Ganglioneuroblastome de l'orbite.

Ganglioneuroblastoma a transitional tumor of sympathetic origin has not yet been described as involving orbit. It is characterized by a mixture of cells ranging from primitive neuroblast to well differentiated ganglion cells within a neurofibromatous tissue. The prognosis is uncertain, as the tumor may either undergo maturation into a ganglioneuroma or may metastasize widely and rapidly as in neuroblastoma. We may postulate a relationship between ganglioneuroblastoma and Recklinghausen's neurofibromatosis in view of the development of the tumor in conjunction with the phacomatosis.